Ptip and the Trr-COMPASS-like Complex Regulate Cardiac Progenitor Cell Division in the Drosophila Embryonic Heart...

The Complex Proteins Associated with Set1 (COMPASS)-like complex regulates developmental gene expression via histone 3 lysine 4 (H3K4) methylation and other transcriptional mechanisms. Several members of the lysine methyltransferase 2C and D (KMT2C/D)-COMPASS-like complex are implicated in human congenital heart and vascular defects. The investigation of the orthologous Trithorax-related (Trr)-COMPASS-like complex in Drosophila melanogaster (the fruit fly) offers a versatile model to explore gene function in the developing heart. Previous studies have demonstrated the importance of the genes encoding complex members in the later stages of heart development and heart function in both insect and mammalian models. In this study, we investigate the function of trr and the complex member PAX transcription activation domain interacting protein (Ptip) within the Drosophila embryonic dorsal vessel (heart tube). The loss of activity of either gene results in cardiac cell division defects in the Tinman (Tin) and Seven up (Svp) lineages. Furthermore, genetic interaction studies identify a strong synergistic interaction between Ptip and trr implicating Ptip-Trr-COMPASS-like complex regulation in cardiac progenitor cell division. Interestingly, global H3K4 mono-methylation (H3K4me1) and di-methylation (H3K4me2) levels were not significantly affected in either Ptip or trr mutants, suggesting that these proteins regulate cardiac target genes at a local scale. In conclusion, these results suggest that the Trr/KMT2C/D-COMPASS-like complex is a key regulator of cardiac progenitor cell division during early embryonic heart development.